A process for producing Compound (I) having the depressor activity or a salt thereof is described, for example, in EP-A-0881212 and EP-A-0459136. However, since Compound (I) is synthesized using an organotin compound, the organotin compound which is difficult to remove remains in the compound. In the process described in EP-A-0881212 and EP-A-0459136, about 2000 ppm (measured by atomic absorption) of a tin compound is contained in Compound (I).
In addition, since the analogues such as 2,3-dihydro-2-oxo-1-[[2′-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxylic acid [hereinafter, referred to as ketone compound in some cases] and ethyl 2-ethoxy-1-[[2′-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimdazole-7-carboxylate [hereinafter, referred to as ethyl ester compound in some cases] have the similar properties to those of Compound (I), it is difficult to remove those analogues, and considerable amounts of them (total: about 3%) are contained in Compound (I). In addition, Compound (I) has the very low solubities in various solvents, this is one of factors making purification of Compound (I) difficult and, for this reason, a mixed solvent of dichloromethane-methanol in which Compound (I) is relatively highly soluble has been previously used in purification. As a result, highly toxic dichloromethane remains in Compound (I) at a few hundreds ppm.
Like this, considerable amounts of a tin compound, analogues and dichloromethane are present in Compound (I) which has been prepared by the conventional process. However, previously, since a preparation product containing Compound (I) as an original drug is not used as a medicament, Compound (I) is derived to (±)-1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[[2′-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxylate [hereinafter, referred to as candesartan cilexetil in some cases] via a number of steps, and a preparation product containing the same compound as an original drug is used as a medicament, the contaminants such as a tin compound, a ketone compound, an ethyl ester compound and dichloromethane are removed via a number of steps, and the presence of these contaminants in Compound (I) was not problematic at all. However, when a preparation product containing Compound (I) as an original drug is developed as a medicament (e.g. injectable), the presence of a tin compound, analogues and dichloromethane at an amount exceeding a tolerable amount becomes a serious problem.
In the conventional process, in order to remove contaminants such as a tin compound, analogues and the like, purification was carried out using a mixed solvent of dichloromethane-methanol. However, for developing a preparation product as a medicament containing Compound (I) as an original drug, the purification efficacy of the conventional process is not sufficient, and a few thousands ppm of a tin compound and a few % of analogues remain even after purification. In addition, since dichloromethane is used as a purification solvent, a few hundreds ppm of dichloromethane remains in Compound (I). Because of the presence of such the tin compound, analogues and dichloromethane at amounts exceeding tolerable amounts, it has previously been difficult to develop a preparation product as a medicament containing compound (I) as an original drug. For this reason, there is desired a process which can afford Compound (I) containing small residual amounts of a tin compound, analogues and dichloromethane which can be employed as a medicament.